The objectives of this project are to determine the factors controlling fatty acid oxidation. Carnitine is an essential cofactor for long chain fatty acid oxidation and may function as an important regulator. The pathway for the biosynthesis of carnitine in the rat has been outlined. We are now characterizing the enzymatic hydroxylation of trimethyllysine to form 3-hydroxybutyrate. We plan to study the conversion of 3-hydroxytrimethyllysine into trimethylaminobutyrate. We plan to investigate the biosynthesis of carnitine during fasting in the rat, a state where carnitine is conserved. High pressure liquid chromatographic methods are under development to determine trimethyllysine, trimethylaminobutyrate, carnitines and acylcarnitines. We are monitoring plasma and urine carnitine and its derivatives in diabetes, following glucagon injection in insulin-dependent diabetics. Carnitine palmitoyltransferase is being purified and the kinetics will be studied. The pathophysiology of lipoid myopathies is providing new directions for study of skeletal muscle fatty acid oxidation.